A genome-wide association study of COPD identifies a susceptibility locus on chromosome 19q13

ICGN Investigators, Michael H Cho, Peter J Castaldi, Emily S Wan, Mateusz Siedlinski, Craig P Hersh, Dawn L Demeo, Blanca E Himes, Jody S Sylvia, Barbara J Klanderman, John P Ziniti, Christoph Lange, Augusto A Litonjua, David Sparrow, Elizabeth A Regan, Barry J Make, John E Hokanson, Tanda Murray, Jacqueline B Hetmanski, Sreekumar G PillaiXiangyang Kong, Wayne H Anderson, Ruth Tal-Singer, David A Lomas, Harvey O Coxson, Lisa D Edwards, William MacNee, Jørgen Vestbo, Julie C Yates, Alvar Agusti, Peter M A Calverley, Bartolome Celli, Courtney Crim, Stephen Rennard, Emiel Wouters, Per Bakke, Amund Gulsvik, James D Crapo, Terri H Beaty, Edwin K Silverman

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

The genetic risk factors for chronic obstructive pulmonary disease (COPD) are still largely unknown. To date, genome-wide association studies (GWASs) of limited size have identified several novel risk loci for COPD at CHRNA3/CHRNA5/IREB2, HHIP and FAM13A; additional loci may be identified through larger studies. We performed a GWAS using a total of 3499 cases and 1922 control subjects from four cohorts: the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE); the Normative Aging Study (NAS) and National Emphysema Treatment Trial (NETT); Bergen, Norway (GenKOLS); and the COPDGene study. Genotyping was performed on Illumina platforms with additional markers imputed using 1000 Genomes data; results were summarized using fixed-effect meta-analysis. We identified a new genome-wide significant locus on chromosome 19q13 (rs7937, OR = 0.74, P = 2.9 × 10(-9)). Genotyping this single nucleotide polymorphism (SNP) and another nearby SNP in linkage disequilibrium (rs2604894) in 2859 subjects from the family-based International COPD Genetics Network study (ICGN) demonstrated supportive evidence for association for COPD (P = 0.28 and 0.11 for rs7937 and rs2604894), pre-bronchodilator FEV(1) (P = 0.08 and 0.04) and severe (GOLD 3&4) COPD (P = 0.09 and 0.017). This region includes RAB4B, EGLN2, MIA and CYP2A6, and has previously been identified in association with cigarette smoking behavior.
Original languageEnglish
Pages (from-to)947-57
Number of pages11
JournalHuman Molecular Genetics
Issue number4
Publication statusPublished - 2012


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